The purpose of this project is to assess the neurological status of individuals who have abused cocaine over a long period of their lives. The acute and chronic use of cocaine is associated with medical and neuropsychiatric abnormalities. The neuropsychiatric disorders include seizure, psychosis, subarachnoid hemorrhage, and thromboembolic phenomena. Most of these abnormalities occur in the acute setting of cocaine use. However, we are aware of no studies which used the detailed classical neurological examination in order to classify possible effects of the drugs on the central (CNS) and peripheral (PNS) nervous system. As a first step towards the elucidation of cocaine effects on the nervous system, we have thus started to carry out thorough neurological examination in subjects who are chronic cocaine abusers and who are seronegative for HIV. Subjects with a long history of cocaine abuse receive a complete medical and neurological examination. The results of these examinations have shown some consistent findings. A total of twenty subjects were evaluated. Four subjects were dropped because of positive autoantibodies. The abnormal findings on the neurological examination included horizontal nystagmus, abnormal eye pursuit, abnormal saccades, decreased reflexes, and increased jaw jerk. Vibration and position senses were also abnormal. The presence of nystagmus and increased jaw jerk in these subjects may be related to cocaine effects on brainstem pathways. The reflex and sensory abnormalities appear to correspond to a bilateral symmetric neuropathy. When taken together, these results suggest that cocaine may cause deleterious effects on the nervous system by causing constriction of the vasa nervorum which supply the PNS. In addition to providing preliminary documentation of the damage done to the PNS by cocaine, these findings suggest a new line of investigation which will focus on the clinical neurological consequences of cocaine abuse.